Abstract: Twenty molecular dynamics (MD) simulations of molecular imprinting prepolymerization systems had been performed to optimize the imprinting shell of the fluorescent sensor. The results revealed that the system with a Bisphenol A (BPA): 3-aminopropyltriethoxysilane (APTES): tetraethylorthosilicate (TEOS) mole ratio of 10:15:60 had the most stable template (T)-functional monomer (FM) cluster. Correspondingly, five kinds of imprinted and non-imprinted polymers were synthesized to assess the reliability and validity of the simulation results. Hybrid SiO2-coated CdTe NCs (HS-QD) were synthesized by a simple reflux procedure including a sol-gel reaction that resulted in the formation of a hybrid SiO2 layer with CdS-like clusters on a CdTe core. Based on the optimal component ratio of the prepolymerization system, MIP shells were anchored on the surface of HS-QD to build a fluorescent MIP sensor. A linear relationship between relative fluorescence intensity and the concentration of BPA had been obtained covering the concentration range of 0.05-10 μmol L-1 with a limit of detection of 6 nmol L-1. The feasibility of the fluorescent sensor was successfully evaluated through the analysis of BPA in river water and milk. The recoveries are above 96.31%, and the relative standard deviation (RSD) ranged from 1.55% to 2.78%Template and target information:bisphenol A, BPAAuthor keywords:Molecularly imprinted polymers, fluorescence quenching, Hybrid SiO2-coated CdTe nanocrystals, Molecular dynamics simulations, bisphenol A